The goals of this group are to identify the structural components of the T cell antigen receptor complex, to attempt to understand the structure of that complex and to relate that structure to how the complex assembles, is transported throughout the endomembrane system and expressed on the cell surface, and, finally, how it actually functions to activate the T lymphocyte. This group has used gene transfection and mutagenesis studies to address and identify the subunit interactions within the eight-chain receptor complex. These studies have led to a model for the structure of the T cell receptor. One of the major themes of this groups has been the identification of specific molecular motifs that are responsible for the assembly, intracellular targeting, and function of the receptor. Major advances have been in the identification of these motifs, and particularly in the identification and characterization of the structural motif responsible for the activation of T cells, and the demonstration that this motif is a repetitive one that is responsible not only for T cell activation, but for B cell activation and for the activation of other cells of the inflammatory system such as the cells responsible for the allergic response, mass cells and basophils. Finally, this group has successfully developed a molecular engineering approach to solve the vexing problem of how to produce large amounts of purified, functional T cell receptor antigen recognition heterodimers. Accomplishing this task utilized the information gathered over the pst several years in this laboratory on the structural motifs involved in both assembly and intracellular targeting. The approach developed appears to be a generally applicable one and the group has successfully expressed multiple human and murine T cell receptors. The group is now in the process of producing milligram quantities of the purified soluble receptor heterodimer for x- ray crystallography studies with Dr. Don Wiley at Harvard University.
